Multiple myeloma (MM), an incurable plasma cell malignancy, requires localisation within the bone marrow in order to survive and proliferate. Interactions between the malignant plasma cell and bone marrow mesenchymal stem cell (BMMSC) are thought to be a critical determinant of this requirement, and include both physical and chemical components. There is increasing evidence that the phenotype of the BMMSC is stably altered in patients with MM. More recently, it has been suggested that this phenotypic transformation is also observed in patients with the benign condition known as monoclonal gammopathy of undetermined significance (MGUS), which almost always precedes MM. In this study, we describe a mechanism by which the peptidyl arginine deiminase 2 (PADI2) enzyme plays an key role in the control of malignant plasma cell phenotype by BMMSCs. PADI enzymes deiminate (citrullinate) peptidyl arginine residues, changing the function or interactions made by the target protein. We identified PADI2 as one of the most highly upregulated transcripts in BMMSCs from both MGUS and MM patients, and that through citrullination of arginine residue 26 of histone H3, it induces the upregulation of interleukin-6 (IL-6) expression. This directly leads to the acquisition of resistance to the chemotherapeutic agent, bortezomib, by malignant plasma cells. We therefore describe a novel mechanism by which BMMSC dysfunction in patients with MGUS and MM directly leads to pro-malignancy signalling through the citrullination of histone H3R26.
Citrullination of histone H3 drives IL-6 production by bone marrow mesenchymal stem cells in MGUS and multiple myeloma.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesPrevalence and severity of allergic diseases have increased worldwide. To date, respiratory allergy phenotypes are not fully characterized and, in addition, the mechanisms underlying sublingual immunotherapy (SLIT) are still unknown.
Exploring novel systemic biomarker approaches in grass-pollen sublingual immunotherapy using omics.
Specimen part, Treatment, Time
View SamplesEpimorphic regeneration is the process by which complete regeneration of a complex structure such as a limb occurs through production of a proliferating blastema. This type of regeneration is rare among vertebrates but does occur in the African clawed frog Xenopus laevis, traditionally a model organism for the study of early development. Xenopus tadpoles can regenerate tails, limb buds and the lens of the eye, although the ability of the latter two organs to regenerate diminishes with advancing developmental stage. Using a heat shock inducible transgene that remains silent unless activated, we have established a stable line of transgenic Xenopus in which the BMP inhibitor Noggin can be over-expressed at any time during development. We have previously shown that activation of this transgene blocks regeneration of the tail and limb of Xenopus tadpoles. In the current study, we have taken advantage of this transgenic line to directly compare gene expression in same stage regenerating vs. non-regenerating hind limb buds. Using Affymetrix gene chip analysis, we have identified genes whose expression levels are linked to regenerative success. These include the BMP inhibitor Gremlin and the stress protein Hsp60 (no blastema in zebrafish). Analysis of overrepresented Gene Ontology functional groupings suggests that successful regeneration in the Xenopus hind limb depends on induction of stress response pathways. Furthermore, as expected, genes involved in embryonic development and growth are also significantly over-represented in regenerating early hind limb buds.
Identification of genes associated with regenerative success of Xenopus laevis hindlimbs.
No sample metadata fields
View SamplesSubpopulations of human fetal thymocyte and circulating nave T cells were obtained through FACS sorting, including CD3-CD4+CD8- intrathymic T progenitor cells (ITTP), CD3intCD4+CD8+ "double positive" thymocytes (DP), CD3highCD4+CD8- "single positive" thymocytes (SP4), CD3+CD4+CD8-CD45RA+CD62L+ nave T cells from cord blood (CB4+), and CD3+CD4+CD8-CD45RA+CD62L+ nave T cells from adult blood (AB4+).
Gene expression profiles during human CD4+ T cell differentiation.
No sample metadata fields
View SamplesOligodendrocytes undergo extensive changes as they differentiate from progenitors into myelinating cells. To better understand the
Identification of a novel oligodendrocyte cell adhesion protein using gene expression profiling.
No sample metadata fields
View SamplesCortical development is a complex process involving the generation of neuronal progenitors, which proliferate and migrate to form the stratified layers of the maturing cortex. To identify microRNAs (miRNAs) and genes that may be important during early cortical development, we analyzed the expression profiles of rat neuronal progenitors obtained at embryonic day 11 (E11), E12 and E13 using microarrays. Neuronal progenitors were purified from telencephalic dissociates with a positive-selection strategy using surface labeling tetanus-toxin and cholera-toxin and fluorescence-activated cell sorting. We identified classes of miRNAs and mRNAs that were up-regulated or down-regulated in these neuronal progenitors as cortical development progressed from E11 to E13. We present data that supports a regulatory role for miRNAs during the transition from neuronal progenitors into differentiating cortical neurons.
Integrating microRNA and mRNA expression profiles of neuronal progenitors to identify regulatory networks underlying the onset of cortical neurogenesis.
No sample metadata fields
View SamplesWe perform microarray analysis of HUVECs upon stimulation with virulent wildtype C. albicans strain SC5314 or its efg1/efg1 cph1/cph1 hyphal-deficient derivative strain CAN34 to compare the gene expression profiles elicited from HUVECs in response to these strains. In addition, these responses are compared to that of TNF-alpha induced responses to determine which responses are Candida-specific.
Transcriptome profile of the vascular endothelial cell response to Candida albicans.
No sample metadata fields
View SamplesExperiment 1: U133A arrays (2) hybridized to duplicate sscDNA samples prepared from 20 ng Clontech UHR RNA
Increased DNA microarray hybridization specificity using sscDNA targets.
No sample metadata fields
View SamplesMicroarray analysis was used to compare the gene expression profiles of Deaf-1-transduced mouse mammary epithelial cells (MECs) relative to Deaf-1-deficient MECs.
Deaf-1 regulates epithelial cell proliferation and side-branching in the mammary gland.
No sample metadata fields
View SamplesTranscriptome profiling using Affymetrix GeneChip arrays was performed on sorted populations of Lgr5-expressing mouse ovarian surface epithelium.
Lgr5 marks stem/progenitor cells in ovary and tubal epithelia.
Sex, Specimen part
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